Quantitative spinal cord (SC) magnetic resonance imaging (MRI) is fraught with challenges, among which is the lack of standardized imaging protocols. Here we present a prospectively harmonized quantitative MRI protocol, which we refer to as the spine generic protocol, for the three main 3T MRI vendors: GE, Philips and Siemens. The protocol provides valuable metrics for assessing SC macrostructural and microstructural integrity: T1-weighted and T2-weighted imaging for SC cross-sectional area (CSA) computation, multi-echo gradient echo for gray matter CSA, as well as magnetization transfer and diffusion weighted imaging for assessing white matter microstructure. The spine generic protocol was used to acquire data across 42 centers in 260 healthy subjects, as detailed in the companion paper [REF-DATA]. The spine generic protocol is open-access and its latest version can be found at: https://spinalcordmri.org/protocols. The protocol will serve as a valuable starting point for researchers and clinicians implementing new SC imaging initiatives. Note to the reviewer/editor/publisher: the companion paper is referred to as [REF-DATA]6/52 121 122dealing with cervical myelopathy and MS populations. Applications of the MethodThe proposed protocol is not geared towards a specific disease and it is suitable for imaging WM pathology (demyelination and Wallerian degeneration via axon/myelin-sensitive 122 https://mssociety.ca/about-ms-research/about-our-research-program/research-we-fund/canadian-prospect ive-cohort-study-to-understand-progression-in-ms-canproco 121 https://www.wingsforlife.com/us/research/imaging-spinal-cord-injury-and-assessing-its-predictive-value-th e-inspired-study-2675/ 9/52

Recently, non-Gaussian diŠusion-weighted imaging (DWI) techniques, including qspace imaging (QSI) and diŠusional kurtosis imaging (DKI), have emerged as advanced methods to evaluate tissue microstructure in vivo using water diŠusion. QSI and DKI have shown promising results in clinical applications, such as in the evaluation of brain tumors (e.g., grading gliomas), degenerative diseases (e.g., speciˆc diagnosis of Parkinson disease), demyelinating diseases (e.g., assessment of normal-appearing tissue of multiple sclerosis), and cerebrovascular diseases (e.g., assessment of the microstructural environment of fresh infarctions). Representative metrics in clinical use are the full width at half maximum, also known as the mean displacement of the probability density function curve, which is derived from QSI, and diŠusional kurtosis, which is derived from DKI. These new metrics may provide information on tissue structure in addition to that provided by conventional Gaussian DWI investigations that use the apparent diŠusion coe‹cient and fractional anisotropy, recognized indices for evaluating disease and normal development in the brain and spine. In some clinical situations, sensitivity for detecting pathological conditions is higher using QSI and DKI than conventional DWI and diŠusion tensor imaging (DTI) because DWI and DTI calculations are based on the assumption that water molecules follow a Gaussian distribution, whereas hindrance of the distribution of water molecules by complex and restricted structures in actual neural tissues produces distributions that are far from Gaussian. We review the technical aspects and clinical applications of QSI and DKI, focusing on clinical use and in vivo studies and highlighting diŠerences from conventional diŠusional metrics.

ObjectivesTo investigate the use of root mean square displacement (RMSD) and mean diffusional kurtosis (DK) metrics of q-space imaging data to estimate spinal cord compression in patients with early cervical spondylosis.MethodsWe studied 50 consecutive patients at our institution (22 male, 28 female; mean age 58 years; age range 20–86 years) who had clinical signs and symptoms suggestive of early clinical stage cervical myelopathy. After conventional magnetic resonance (MR) imaging, diffusion tensor and q-space image data were acquired using 3-T MR imaging. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), RMSD and mean DK values were calculated and compared between compressed and uncompressed spinal cords.ResultsFA and mean DK values were significantly lower and RMSD was significantly higher (P = 0.0060, 0.0020 and 0.0062, respectively; Mann–Whitney U test with the Bonferroni correction) in compressed spinal cords than in uncompressed cords. ADC was also higher in compressed cords, but this difference was not statistically significant.ConclusionsIn the evaluation of spinal cord damage in early cervical spondylosis, mean DK and RMSD values in the spinal cord may be highly sensitive indicators of microstructural change and damage.Key Points• Absolute surgical indications for cervical spondylosis with myelopathy remain to be established.• Diffusion tensor MRI shows abnormalities in normal-appearing but compressed spinal cord.• Non-Gaussian diffusion analysis is highly sensitive in revealing spinal cord damage.

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Background Previous quantitative synthetic MRI of the brain has been solely performed in 2D. Purpose To evaluate the feasibility of the recently developed sequence 3D‐QALAS for brain cortical thickness and volumetric analysis. Study Type Reproducibility/repeatability study. Subjects Twenty‐one healthy volunteers (35.6 ± 13.8 years). Field Strength/Sequence 3D T1‐weighted fast spoiled gradient recalled echo (FSPGR) sequence was performed once, and 3D‐QALAS sequence was performed twice with a 3T scanner. Assessment FreeSurfer and FIRST were used to measure cortical thickness and volume of subcortical structures, respectively. Agreement with FSPGR and scan–rescan repeatability were evaluated for 3D‐QALAS. Statistical Tests Percent relative difference and intraclass correlation coefficient (ICC) were used to assess reproducibility and scan–rescan repeatability of the 3D‐QALAS sequence‐derived measurements. Results Percent relative difference compared with FSPGR in cortical thickness of the whole cortex was 3.1%, and 89% of the regional areas showed less than 10% relative difference in cortical thickness. The mean ICC across all regions was 0.65, and 74% of the structures showed substantial to almost perfect agreement. For volumes of subcortical structures, the median percent relative differences were lower than 10% across all subcortical structures, except for the accumbens area, and all structures showed ICCs of substantial to almost perfect agreement. For the scan–rescan test, percent relative difference in cortical thickness of the whole cortex was 2.3%, and 97% of the regional areas showed less than 10% relative difference in cortical thickness. The mean ICC across all regions was 0.73, and 80% showed substantial to almost perfect agreement. For volumes of subcortical structures, relative differences were less than 10% across all subcortical structures except for the accumbens area, and all structures showed ICCs of substantial to almost perfect agreement. Data Conclusion 3D‐QALAS could be reliably used for measuring cortical thickness and subcortical volumes in most brain regions. Level of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1834–1842.

Mapping of MR fiber g-ratio, which is the ratio of the diameter of the axon to the diameter of the neuronal fiber, is introduced in this article. We investigated the MR fiber g-ratio, the axon volume fraction (AVF) and the myelin volume fraction (MVF) to evaluate microstructural changes in the spinal cord in patients with cervical spondylotic myelopathy (CSM) in vivo, using atlas-based analysis. We used diffusion MRI data acquired with a new simultaneous multi-slice accelerated readout-segmented echo planar imaging sequence for diffusion analysis for AVF calculation and magnetization transfer saturation imaging for MVF calculation. The AVFs of fasciculus gracilis in the affected side spinal cord, fasciculus cuneatus and lateral corticospinal tracts (LSCT) in the affected and unaffected side spinal cord were significantly lower (P = 0.019, 0.001, 0019, 0.000, and 0.002, respectively) than those of normal controls. No difference was found in the MVFs. The fiber g-ratio of LSCT was significantly lower (P = 0.040) in the affected side spinal cords than in the normal controls. The pathological microstructural changes in the spinal cord in patients with CSM, presumably partial axonal degenerations with preserved myelin. This technique has the potential to be a clinical biomarker in patients with CSM in vivo.

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